Table 1 Summary of dark regions overlapping genome-wide significant loci from GWAS studies
From: Investigating the dark-side of the genome: a barrier to human disease variant discovery?
GWAS Disorder | FUMA ID | Genomic risk loci (GRL) | Mapped genes (MGs) | # MGs with dark CDS | GO enrichment | |||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
# GRLs | # GRLs overlapping DRs | % GRLs overlapped by DRs | Overlap (bp) | # MGs | # MGs overlapping DRs | % MGs overlapping DRs | Overlap (bp) | Any | > 5% | > 20% | All dark GWAS MGs vs Genome | Relevant Gene Ontology enrichment terms (biological processes) | GWAS MGs with Dark CDS vs remaining GWAS | Relevant Gene Ontology enrichment terms | ||
ASD | 10 | 3 | 1 GRL (1 DR) | 33 | 92 bp | 113 | 8 (37 DRs) | 7 | 12 Kb | 0 | 0 | 0 | 106 terms (p < 0.05) | Neuron differentiation, ERBB signalling pathway | – | – |
SCZ | 323 | 242 | 109 GRL (1617 DRs) | 45 | 1075 Kb | 879 | 176 (962 DRs) | 20 | 433 Kb | 21 | 15 | 10 | 17 terms (FDR sig) | Terms related to neurogenesis; synapse (structure and signalling); and calcium ion transport | 6 | Striatal medium spiny neuron differentiation; striatum development; sub-pallium development; forebrain neuron differentiation; and forebrain generation of neurons |
BMI | 221 | 832 | 430 GRL (3427 DRs) | 52 | 1317 Kb | 8663 | 1545 (5322 DRs) | 18 | 1902 Kb | 133 | 83 | 41 | 228 terms (FDR sig) | Terms related to cell morphogenesis, development and differentiation; signalling, signal transduction and cell communication; cell migration and motility, localization, cell adhesion and cell junction organization; neurogenesis, neuron development and differentiation; and immune response | 35 | SMAD protein phosphorylation; sex determination; steroid biosynthesis; muscle morphogenesis; transmembrane receptor protein serine/threonine kinase signaling pathway; and GABAergic synaptic transmission |
BD | 192 | 16 | 9 GRL (157 DRs) | 56 | 77 Kb | 293 | 45 (168 DRs) | 15 | 86 Kb | 6 | 5 | 3 | 160 terms (p < 0.05) | Terms related to synaptic structure and function plasticity; action potential; central nervous system and brain development; and myelination | – | – |
MDD | 191 | 51 | 22 GRL (144 DRs) | 43 | 99 Kb | 645 | 116 (426 DRs) | 18 | 121 Kb | 8 | 3 | 0 | 45 terms (FDR sig) | Terms related to neurogenesis; synaptic function; neurotransmitter transport; and nervous system development | 40 | Presynaptic active zone assembly; protein localization to synapse; pre-synapse organization; and pre-synapse assembly |
Cholesterol | 113 | 56 | 28 GRL (130 DRs) | 50 | 49 Kb | 285 | 42 (106 DRs) | 15 | 35 Kb | 6 | 3 | 2 | 433 terms (p < 0.05) | Phospholipid homeostasis; reverse cholesterol transport; monocarboxylic acid biosynthetic process; and carboxylic acid metabolic process | – | – |
ALS | 423 | 11 | 8 GRL (41 DRs) | 73 | 16 Kb | 141 | 18 (46 DRs) | 13 | 21 Kb | 2 | 2 | 1 | 185 terms (p < 0.05) | Membrane trafficking, signal transduction and ion channel transport; autophagy; central nervous system and oligodendrite development; dopaminergic neuron differentiation, neuron maturation, regulation of cell differentiation; central nervous system myelination and axon ensheathment and neuron axonogenesis | – | – |
Crohn's disease | 2 | 71 | 27 GRL (470 DRs) | 38 | 212 Kb | 276 | 47 (228 DRs) | 17 | 97 Kb | 7 | 5 | 5 | 438 terms (p < 0.05) | Terms related to immune response; cytokine activity; receptors and signalling; and glutamine metabolism | – | – |